One Is Not Enough: Palmoplantar Keratodermas Due to Haploinsufficiency of AAGAB

Mutations that affect cell division and epidermal growth factor receptor expression are implicated in punctate PPK.

The palmoplantar keratodermas (PPK) present a vexing array of clinical and genetic findings. Pohler and colleagues studied 18 families with autosomal dominant punctuate PPK and identified mutations in the AAGAB gene, which encodes the p34 protein. This protein is thought to function as a regulator of intracellular vesicle transport involved in protein turnover and localization.

Multiple inactivating mutations were identified, all inherited in the heterozygous state. In cells from PPK lesions, the second copy of AAGAB was always normal. Cells expressing mutant p34 bore ultrastructural hallmarks of defective vesicle and protein transport. Inhibition of AAGAB expression in keratinocytes led to marked cell proliferation and remarkably higher lev…

Reviewing Author

Kenneth Y. Tsai, MD, PhD

Disclosures

Grant / Research support American Association for Cancer Research – Landon Foundation; National Institutes of Health/National Cancer Institute; Cancer Prevention Research Institute of Texas

Editorial BoardsJournal of the American Academy of Dermatology

Kenneth Y. Tsai, MD, PhD

Disclosures

Grant / Research support American Association for Cancer Research – Landon Foundation; National Institutes of Health/National Cancer Institute; Cancer Prevention Research Institute of Texas

Editorial BoardsJournal of the American Academy of Dermatology